This proposal describes a 5-year program for the development of an academic career in lower urinary tract physiology. The Candidate has a background in smooth muscle physiology, and completed doctoral training in Pharmacology and Toxicology under the mentorship of Drs. Stephanie Watts and William Jackson (Michigan State University). He then came to the University of Vermont as a Postdoctoral Fellow to begin a path toward an independent research career. He now combines his strengths in smooth muscle physiology and vascular pharmacology to create a novel proposal investigating bladder blood flow as it relates to bladder dysfunction in diabetes. Nearly half of all diabetic patients experience lower urinary tract symptoms (LUTS), which significantly reduce their quality of life. Although ample evidence links impaired bladder blood flow to LUTS, a fundamental gap exists in our understanding of bladder blood flow regulation and its effects on bladder function. The goals of this project are to understand how the unique properties of the urinary bladder vasculature regulate bladder function. Furthermore, this project will investigate if decreased blood flow leads to bladder dysfunction in diabetes, with a specific focus on signaling mechanisms that regulate vessel tone in bladder arterioles. This hypothesis-driven research project will allow the applicant to develop skills in state-of- the art in vitro and in vivo physioogy methods, including electrophysiology, diameter and membrane potential measurements in isolated blood vessels, and in vivo urodynamic measurements, that will provide unprecedented detail into vascular function in the urinary bladder during diabetes. The results could potentially re-frame LUTS treatment to include both vascular and neurological therapeutic interventions. The University of Vermont (UVM) is internationally recognized for its strength in smooth muscle biology, with unique expertise in both vascular and urinary bladder physiology. Mark Nelson, Ph.D. will mentor the Candidate's scientific development. Dr. Nelson is a recognized leader in the field of vascular biology and bladder physiology and has trained numerous postdoctoral fellows and graduate students, many of whom are now established independent investigators. To enhance the Candidate's training, the program enlists the expertise of a mentoring committee, including Drs. Joseph Brayden, George Wellman, Margaret Vizzard and Mark Plante. Dr. Brayden pioneered techniques for the study of vascular smooth muscle membrane potential. Dr. Wellman adds expertise in K+ channel function and electrophysiology. Dr. Vizzard brings substantial experience with bladder research and in vivo conscious cystometry. Dr. Plante is a successful clinical urologist with perspectives on translational science and research. This research environment maximizes the potential for the Candidate to establish a scientific niche from which an academic career can be constructed. This project will facilitate continued technical, intellectual, and professional training of the Candidate, and will assist the Candidate in the establishment of an independent research laboratory at an academic research institution.